Tetrahedron Letters, 1999, 40, 2605-2606 discloses preparation of 1-phenyl-3-bromopyrazole-5-carboxylic acid derivatives involving generation of a reactive bromonitrilimine intermediate. Cycloaddition of this intermediate with an acrylic ester gives a 1-phenyl-3-bromo-2-pyrazoline-5-carboxylate ester, which can be subsequently oxidized to the desired 1-phenyl-3-bromo-2-pyrazole-5-carboxylate ester. Alternatively, cycloaddition with a propiolate ester gives the 1-phenyl-3-bromo-2-pyrazole-5-carboxylate ester directly.
U.S. Pat. No. 3,153,654 discloses condensation of certain optionally substituted aryl (e.g. phenyl or naphthyl which are optionally substituted with lower alkyl, lower alkoxy or halogen) hydrazines with certain fumaric or maleic esters to provide 3-pyrazolidinone carboxylic acid derivatives.
Japanese Unexamined Patent Publications 9-316055 and 9-176124 disclose production of pyrazole carboxylic acid ester derivatives and pyrazoline derivatives, respectively, which are substituted with alkyl at the 1-position.
J. Med. Chem. 2001, 44, 566-578 discloses a preparation of 1-(3-cyanophenyl)-3-methyl-1H-pyrazol-5-carboxylic acid and its use in preparing inhibitors of blood coagulation factor Xa.
The present invention provides technology useful for conveniently preparing 3-halo-5-carboxylate-1-aryl-substituted dihydro-1H-pyrazoles and pyrazoles.